Alcohol use during pregnancy remains a problem despite education regarding the detrimental effects of alcohol, including neurodevelopmental delays and increased risk for infection, on the unborn child. One of the obstacles in this field of research is the under-reporting, by mothers, of alcohol use during pregnancy due to the fear of repercussions and social stigma. Until recently, a clear biomarker of prenatal exposure to alcohol had not been established. Ongoing studies now show that Fatty Acid Ethyl Esters (FAEE), non-oxidative by- products of alcohol metabolism, detected in meconium and hair samples are useful indicators of in utero alcohol exposure in full term newborns. Despite this, studies were not carried out in preterm newborns. Therefore, there is still very limited research on the effects of prenatal alcohol exposure on the premature newborn and specifically the premature developing lung. The studies outlined in this proposal will determine if prenatal alcohol exposure increases the accumulation of cytotoxic Fatty Acid Ethyl Esters (FAEE) in the lungs of our preterm guinea pig animal model (Aim 1). Then, we will examine whether the accumulation of these Fatty Acid Ethyl Esters affects the function of the lung's immune cells, alveolar macrophages, which are the first line of defense against infection in the lung (Aim 2). These hypotheses will be examined by performing various experiments on in utero ETOH-exposed preterm guinea pigs and control animals. We will evaluate the presence of FAEE in the lung tissue and macrophages, determine whether these FAEE affect lung macrophages'function or viability, and whether certain FAEE are more harmful than others. These results could elucidate a novel mechanism of how prenatal alcohol exposure increases the premature newborn's risk for infection and lung injury. This information will eventually aid in the identification of possible therapeutic interventions to protect the exposed premature newborn from respiratory infections and infection-mediated morbidity and mortality. Using the support from this NRSA grant, the guidance of well established research mentors, and the opportunities and resources available at Emory University and the Emory Alcohol and Lung Biology Center, the upcoming year of post-doctoral training will be used to expand my knowledge of research design/grant and manuscript writing, refine investigative skills, and learn new techniques in the lab. This time will also allow for the integration of my research and clinical career and the opportunity to obtain data which will be utilized to apply for long-term, NIH sponsored career development funding. This year will prepare me for my long-term goal of becoming a successful independent academic researcher in the field of neonatal research. PUBLIC HEALTH RELEVANCE: Alcohol use during pregnancy, which results in a significant proportion of both premature and term newborn infants born with prenatal alcohol-exposure, remains a problem despite public announcements regarding the detrimental effects of alcohol on the unborn child. Despite this, there is very limited research on the effects of prenatal alcohol exposure on the premature newborn so, in an effort to address this issue, this proposal will determine if prenatal alcohol exposure increases the accumulation of cytotoxic Fatty Acid Ethyl Esters (FAEE) in the lungs of our preterm guinea pig animal model and whether these FAEE affect alveolar macrophage function. These results could elucidate whether prenatal alcohol exposure adds to the premature newborn's already increased risk for infection and lung injury.